14-99645226-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001127258.3(HHIPL1):​c.19G>C​(p.Gly7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 34)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

HHIPL1
NM_001127258.3 missense

Scores

1
3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.264
Variant links:
Genes affected
HHIPL1 (HGNC:19710): (HHIP like 1) This gene encodes a protein that belongs to the glucose/sorbosone dehydrogenase family. The encoded protein also contains a domain that binds folate and reduced folic acid derivatives. [provided by RefSeq, Jul 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19164687).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HHIPL1NM_001127258.3 linkc.19G>C p.Gly7Arg missense_variant Exon 1 of 9 ENST00000330710.10 NP_001120730.1 Q96JK4-1F1T0G3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HHIPL1ENST00000330710.10 linkc.19G>C p.Gly7Arg missense_variant Exon 1 of 9 1 NM_001127258.3 ENSP00000330601.5 Q96JK4-1
HHIPL1ENST00000357223.2 linkc.19G>C p.Gly7Arg missense_variant Exon 1 of 8 1 ENSP00000349757.2 Q96JK4-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152092
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1172012
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
566126
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152092
Hom.:
0
Cov.:
34
AF XY:
0.0000135
AC XY:
1
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000224
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.37
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.023
T;.
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.017
N
LIST_S2
Benign
0.50
T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-0.57
N;N
REVEL
Benign
0.058
Sift
Uncertain
0.021
D;T
Sift4G
Benign
0.14
T;T
Polyphen
0.93
P;P
Vest4
0.25
MutPred
0.40
Gain of methylation at G7 (P = 0.0024);Gain of methylation at G7 (P = 0.0024);
MVP
0.33
MPC
0.49
ClinPred
0.62
D
GERP RS
2.2
Varity_R
0.14
gMVP
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1354072292; hg19: chr14-100111563; API